Since the first anecdotal evidence that nutritional therapy may slow the progression of chronic renal failure (see Walser M., "Ketoacids in the Treatment of Uremia," Clinical Nephrology, 3:180-187 (1975)), there has been growing interest in two possibilities: (1) that a common mechanism causes progression of many types of chronic renal failure, and (2) that this process can be slowed or arrested by diet or drugs.
Many mechanisms of progression have been postulated, based on experiments in animals and/or clinical observations. Factors proposed to contribute to progression include arterial pressure, and more specifically, glomerular capillary pressure which is reduced by angiotensin-converting enzyme inhibitors; serum calcium times phosphorus product; urinary phosphorus excretion; protein intake itself; hyperuricemia; hypertriglyceridemia; hypercholesterolemia; and hyperoxalemia.
Ketoacid mixtures, administered in conjunction with a low protein, low phosphorus diet, have been reported to slow progression in several studies, see Mitch, W. E., et al., "The Effect of a Keto Acid-Amino Acid Supplement to a Restricted Diet on the Progression of Chronic Renal Failure," New England Journal of Medicine, 311:623-629 (1984); Gretz, N., et al., "Low-Protein Diet Supplemented by Ketoacids in Chronic Renal Failure: A Prospective Study," Kidney International, 24, Suppl. 16:S263-S267 (1983); and Barsotti, G., et al., "Effects on Renal Function of a Low-Nitrogen Diet Supplemented with Essential Amino Acids and Keto Analogs and of Hemodialysis and Free Protein Supply in Patients with Chronic Renal Failure," Nephron 27:113-117 (1981), but see Burns, J , et al., "Comparison of the Effects of Ketoacid Analogs and Essential Amino Acids on Nitrogen Homeostasis in Uremic Patients on Moderately Protein-Restricted Diets," American Journal of Clinical Nutrition, 31:1767-1775 (1978).
However, in most of these reports, no attempt was made to differentiate between the effects of the diet and the ketoacids. More recently, it has been reported that some patients progressing on this diet supplemented with essential amino acids exhibit slowed or arrested progression when changed to ketoacids, suggesting a specific effect of ketoacids on progression, see Walser, M , et al., "Progression of Chronic Renal Failure on Substituting a Ketoacid Supplement for an Amino Acid Supplement," J. Amer. Soc. Nephrol., 2:1178-1185 (1992). However, in these studies, compliance with a restrictive diet was required.
Although much research has been done, a need still exists for treatment methods which retard, i.e., slow or arrest, the progression of chronic renal failure and do not require dietary compliance.